Neuropeptides, small signal peptides largely known for their role as transmitters of nerve impulses in the brain which mediate mood and emotion, have now been shown to regulate immune system function. Our work reveals that human monocytes have receptors and will respond chemotactically to numerous neuropeptide. Neuropeptides which we have reported on include 2-endorphin and other opiates, substance P and bombesin. We have shown that a major class of psychoactive drugs, the benzodiazepines, are also potent chemoattractants. In this case we have directly demonstrated the presence of chemotactic receptors through ligand binding experiments. The presence of multiple, diverse, neuropeptide chemotactic receptors on monocytes and other immune system cells suggests the existence of a neuroendocrine link between the brain and the immune system whose purpose is to integrate behavioral and emotional responses with immune system function. In addition to the presence of neuropeptide receptors we have also been able to demonstrate that human aveolar macrophages store and secrete the neuropeptide bombesin. Neuropeptide synthesis may therefore be a general feature of various immune cell populations. Although speculative, such results are consistant with the possibility of a multi-direc-tional communication network via neuropeptides and their receptors. The purpose of such a network would be to link the body's cellular defense and repair systems with the nervous and endocrine systems and thereby integrate the internal millien of the entire organism. Additional work has suggested that a major cause of human cancer, small cell lung carcinoma, may not, as previously thought, arise from lung epithelium but originates from hemopoietic cells when the normal macrophage mediated repair of lung tissue is deranged by continouous heavy smoking. This work represents a major conceptual shift in the understanding of this disease as well as other cancers in which there exists an in flammatory component and suggests novel strategies for disease control with clinical implications.